Determining which patients who present with a suspected acute infection will require antibiotics is a common yet challenging medical decision. Identifying which infection is from a bacterial source versus a viral trigger is difficult in the erly stages of care. Clinical phenotypes widely overlap and current diagnostics are inadequate, leading all too commonly to a default decision to prescribe antibiotics. Consequently, antibiotic overuse and subsequent resistance have become major public health threats. There is a clear need for better strategies to safely reduce antibiotic overuse. One potential approach is to guide the antibiotic decision with results from a prospective serum biomarker test. This approach of tying the therapeutic choice to a biomarker test that identifies the patients most likely to benefi (sometimes called 'theragnostics') has had important success in oncology and cardiology. In infection and sepsis, based on extensive work by our group and others, we believe procalcitonin is the biomarker most ready for a large US trial. Procalcitonin is a calcitonin precursor elevated in bacterial, but not viral, infection. The recent development of a highly sensitive procalcitonin assay has led to multiple studies suggesting procalcitonin has superior performance for detection of bacterial infection compared to traditional markers such as white blood cell count. Initial European trials testing the ability of procalcitonin to improve antibiotic prescription practices have been promising, but key questions of generalizability and safety preclude widespread application. We propose ProACT (Procalcitonin Antibiotic Consensus Trial), a 1514 subject, eight site, randomized trial to test implementation of a procalcitonin antibiotic algorith to safely reduce antibiotic initiation in lower respiratory tract infection (LRTI). We target emergency department (ED) patients as a large proportion of LRTI presents to the ED, and although antibiotic prescription for respiratory infection in primary care has declined, this has nt occurred in EDs. LRTI is a major public health burden and typifies the decision-making challenges of acute infection. Study findings will have an immediate impact on routine ED care of this common condition and could significantly reduce antibiotic use and resistance. This planning grant application proposes to conduct multiple trial preparation activities to facilitate conduct of the full trial.